Type 2 diabetes mellitus (T2DM) afflicts 14 million patients; many patients have undiagnosed gastroparesis (GP) and suffer from nausea, bloating, and abdominal discomfort. Broad objectives of this study are to: 1) determine the prevalence and heritable components of gastric motility abnormalities (e.g. GP, gastric dysrhythmias) and dyspepsia-like symptoms in sibling pairs with T2DM; 2) investigate mechanisms of dyspepsia symptoms and gastric motility dysfunction during acute provocative test meals; and 3) determine the effect of treatment of hyperglycemia on dyspepsia symptoms and gastric motility disorders. Specific aims are: 1) to determine the prevalence of dyspepsia symptoms, GP, and gastric dysrhythmias in a large, well- characterized, community-based population of sibling pairs with T2DM currently enrolled in an NIH sponsored study; 2) to correlate demographics, symptoms, laboratory results, gastric motility test data, and hereditable components in sibling pairs with T2DM with and without GP; 3) to investigate mechanisms of GP and dyspepsia symptoms by measuring gastric myoelectrical activity and selected hormones (e.g., ghrelin, cholecystokinin, and vasopressin) in response to provocative test meals; and 4) to determine the effect of aggressive glucose control on dyspepsia symptoms and gastric motility function. Research design incorporates the recruitment of 200 sibling pairs from a data base of 1200 well-characterized T2DM patients. Symptom questionnaires, solid-phase gastric emptying studies and electrogastrogram recordings with provocative test meal will be completed over the 5 year period (Long-Term Study). Results from these studies will determine the prevalence of gastropathies and dyspepsia symptoms in a comprehensive study of a large population with T2DM. A subset of T2DM patients with and without GP will undergo non-invasive physiologic testing and hormone assays during a provocative water load test and a caloric meal test. Results of these studies will provide new insights into postprandial symptoms in patients with T2DM with and without GP. In the Short-Term Study, patients with GP and HbA1c >8 will be treated aggressively to obtain normal glucose levels and HbA1c levels during a 6 month time period and compared with T2DM patients with normal gastric emptying and HbA1C <8. Electrogastrogram testing with non-caloric and caloric meal tests will be repeated after 3 and 6 months and solid-phase gastric emptying tests after 6 months of therapy. Results from the Short-Term Study will indicate the relevance of hyperglycemia on symptoms, gastric dysrhythmias, and GP in patients with T2DM. There is an epidemic of T2DM in the United States and many patients have unrecognized stomach motility disorders. The proposed research will determine prevalence of the "diabetic stomach" in patients with T2DM, investigate mechanisms of dyspepsia symptoms and stomach neuromuscular dysfunction, and evaluate the role of hyperglycemia in stomach motility dysfunction.